Tissue infection and systemic sepsis are common causes of morbidity and late mortality after major thoracic trauma. To seek causative mechanisms, prognostic indicators, and areas of possible improvement in therapy, we reviewed 310 consecutive adults admitted with major thoracic trauma. Of these, 56 (18%) died of massive injuries in the first 5 days; the remaining 254 were considered at risk for infectious complications. There were 21 late deaths in this group, and 15 (71%) were caused by systemic sepsis. Eighty-four patients (33%) developed thoracic infections, and 15 (6%) had significant nonthoracic infections. Markers of increased risk of infection included blunt injury, shock and unconsciousness on arrival, and splenectomy. Pulmonary infection was increased significantly following prolonged endotracheal intubation, but was virtually absent following tracheostomy. The risk of infection was increased significantly if prophylactic antibiotics were not used, but no definite correlation could be made to advanced age, pre-existent disease, nor post-traumatic malnutrition. Attention to some of these factors may decrease the risk of infection in thoracic trauma.